1. Field of the Invention
The invention relates to an apparatus for extracting and isolating growth factors from platelets and, more particularly, method, apparatus, and kit for obtaining a wound healing composition of growth factors released from mammalian platelet membranes for use in wound healing and other therapeutic uses.
2. Description of the Prior Art
Various devices for collecting and utilizing blood, blood products, plasma, platelets, bone graft materials, and other similar substances are known. U.S. Pat. No. 7,172,071 discloses a method and apparatus for packaging, reconstituting, and delivering bone graft material. The device includes a first container and a second container. The first container maintains the bone graft material at a vacuum, while providing a favorable negative pressure during reconstitution. The device also reconstitutes bone graft under a negative pressure when a reconstituting liquid is injected into a container that is separated from a second container by a gas permeable membrane.
Devices for collecting blood, blood products, plasma, and platelets include devices that are used in the autologous transfusion of blood, autotransfusion systems, cardiotomy reservoirs, and other similar systems. Several patents and patent publications disclose devices or systems for collecting blood that include chambers that have the ability to communicate with vacuum sources.
U.S. Pat. No. 6,508,778 discloses a system for withdrawing blood. The system includes a rigid canister that connects to a vacuum source, a tubing set that includes a stopcock, and a source of anticoagulant that connects to the tubing set. Canadian Patent No. 2,235,722 discloses a rigid canister.
U.S. Pat. No. 6,964,646 discloses a device that is used in the autologous transfusion of blood. The device includes a collecting tank and a vacuum source that connects to the collecting tank.
U.S. Pat. No. 5,785,700 discloses an autotransfusion system including a rigid receptacle carrying a blood collection bag internally and a manually operable portable vacuum source (MOPVS) also carried by the rigid receptacle. The system may be configured in a blood collection mode wherein the MOPVS is in flow communication with the interstitial space between the collection bag and the rigid receptacle to cause a negative pressure therein to draw blood from the patient's wound. In a reinfusion mode, the MOPVS is disconnected from the rigid receptacle and is directly connected to the drain tube leading to the patient to drain unwanted fluid from the patient's wound. The rigid receptacle is inverted and connected to a transfusion line to reinfuse the blood collected within the blood collection bag. The interstitial space is vented to ambient pressure such that the blood within the collection bag is reinfused under force of gravity alone. A hydrophobic vent is connected to the flexible collection bag to vent air collected within the bag to the interstitial space.
U.S. Pat. Nos. 5,374,257 and 5,484,428 disclose a fluid collection container for collecting blood under the influence of a vacuum. The fluid collection container includes a rigid front wall and a flexible rear wall. In a distended configuration, liquid and gaseous fluid flow from the body cavity or wound being drained under the influence of vacuum into the collection container. In a collapsed configuration, the flexible rear wall is foldable relative to the rigid front wall to allow the collected liquid fluids to be reinfused to the patient.
U.S. Pat. No. 3,768,653 discloses a cardiotomy reservoir for recovering patient blood in a surgical procedure. The reservoir includes a uniform tubular case having a base plate and a top plate that provide an enclosed reservoir volume. A blood inlet conduit provides blood to the reservoir. A filtered air exit conduit allows air to flow out of the reservoir. All of the components are physiologically compatible with patient blood.
U.S. Patent Publication No. 2005/0109716 discloses a blood collection and separation system. The system has the ability to connect to a vacuum system.
U.S. Pat. No. 5,192,439 discloses a blood collection reservoir and filter device. The device connects to a vacuum source.
U.S. Pat. No. 6,613,035 discloses an autotransfusion system that includes a collection chamber and a vacuum source.
U.S. Pat. No. 5,304,164 discloses an apparatus for handling a patient's blood during a medical procedure having a reservoir.
U.S. Patent Publication No. 2006/0142707 discloses a system that is used for autologous normovolemic hemodilution. The system includes a canister that holds a bag for collecting blood. The canister includes an inlet that communicates with a vacuum source for evacuating the space between the bag and an internal wall of the canister.
Blood, blood products, plasma, platelets, and other similar substances are very important to the wound healing process. The wound healing process is generally considered to occur in several stages, generally known as the healing cascade. After tissue injury, platelets are among the first cells to appear in the vicinity of the wound. Activation of a platelet by an agonist, such as thrombin, or other agonists known in the art, leads to the release of granule material from within the platelet. Such granulation activation results in the release of proteins known as growth factors, primarily concentrated in the alpha granules of platelets. Released growth factors stimulate the formation of new tissue.
When applied to wounds, growth factors are known to increase the rate of collagen laydown, vascular ingrowth, fibroblast proliferation and overall healing. The release of a protein known as platelet-derived growth factor (PDGF) is a chemotactic signal for monocytes, neutrophils and fibroblasts which then move into the wound to begin the inflammatory stage of the healing process. During this time, monocytes secrete a number of factors, including PDGF and transforming growth factor-beta 1 (TGF-β1) (also found in platelets). In this manner fibroblasts are activated to begin the repair stage of the healing process. Subsequently, wound healing continues through the process of collagen remodeling within the wound.
The term “therapeutically effective amount” refers to the amount or amounts of the constituent bioactive elements or combination thereof necessary to enhance wound healing. Examples of wound healing include the reduction in the volume or surface area of a wound, the increase in the amount of granulation tissue or other biological material facilitating collagen laydown, vascular ingrowth, fibroblast proliferation or overall healing.
Several patents and patent applications are directed to negative pressure therapy, which utilizes growth factors that are naturally present in a wound to promote wound healing. U.S. Pat. No. 6,071,267 discloses a fluid management interface system. The system includes a subsystem that functions to extract fluids, including the patient's blood, serum, etc., from an interface system. The subsystem also introduces various fluids, such as antibiotics, analgesics and growth factors into the interface system. The system also communicates with a vacuum source.
U.S. Pat. Nos. 5,636,643, 5,645,081, 7,198,046, and 7,216,651 disclose a method for treating tissue damage with negative pressure to a wound. The method utilizes a fluid impermeable wound cover that is sealed over a wound site. A screen in the form of an open-cell foam screen or a rigid porous screen is placed between the wound cover and the wound. A vacuum pump supplies suction to the wound cover over the treatment site.
U.S. Pat. Nos. 7,534,240 and 7,553,306 disclose a method and apparatus for treating a wound using negative pressure therapy. The method and apparatus utilizes a foam pad that is in fluid communication with a vacuum source. The foam pad is predisposed with basic fibroblast growth factors or other factors.
U.S. Patent Publication No. 2002/0115952 discloses a biocompatible wound dressing that is used in negative pressure therapy. The wound dressing includes a biocompatible pad and an air-tight seal. The pad must be in fluid communication with a negative pressure source.
U.S. Patent Publication Nos. 2009/0012482 and 2009/0076467 disclose a device that is used in negative pressure therapy. The device includes a sealant layer that encloses a wound and a suction apparatus that reduces the pressure within the enclosure. Optionally, the device includes a collection chamber that is designed to collect exudate or necrotic debris.
It is known to use activated autologous platelets as a treatment in a number of medical and surgical procedures, including but not limited to oral and maxillofacial surgery, orthopedic surgery, cosmetic and reconstructive surgery, chronic tissue repair, sports medicine injuries, neurosurgery, cardiovascular surgery, podiatry, hair transplant surgery, medical research, tissue engineering, and non-surgical cellular therapy.
U.S. Pat. Nos. 4,957,742 and 6,649,072 disclose wound healing compositions that include platelet enriched plasma which prior to use is activated by thrombin to release growth factors from the alpha granules of the platelets.
Unlike negative pressure therapy, which is an in vivo process, there is some interest in extracting platelets or other similar substances for therapeutic purposes. However, extracting therapeutic levels of platelets has been a technical challenge requiring trained cardiovascular perfusionists to operate the equipment originally designed for the production of platelet rich plasma (PRP). The clinical practitioner now has access to more simplified equipment that allows him to process PRP with smaller amounts of whole blood in a shorter amount of time. Venous access, clinical expertise, and cost are still challenges that have limited the widespread use of this process throughout the world. Moreover from a commercial standpoint, wound healing compositions that include platelets must meet costly FDA guidelines applicable to blood products.
Growth factors are responsible for the wound healing process, as described above. Platelets function merely as carriers for the growth factors. Therefore, there is a need for an inexpensive and efficient process for extracting and isolating growth factors from the platelets contained in plasma for subsequent use in wound healing. The final product preferably may be free of other components that are typically found in conventional platelet enriched wound healing products, namely the platelets themselves, ghost platelets, white blood cells, red blood cells, bacteria, and other cellular debris.
It is further desirable to prepare a wound healing product that can be subjected to conventional preservations, such as lyophilization, freeze drying, and cryopreservation in a process that does not destroy the growth factors. In this manner the shelf life of the product would be prolonged.
Therefore, there is a need for a process for isolating and extracting growth factors in a non-destructive manner from platelets. The resulting composition may or may not be substantially free of other components, such as platelets, ghost platelets, white blood cells, red blood cells and bacteria, and can be used immediately fresh or lyophilized or freeze dried into a shelf-stable product for subsequent use.